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氧化 DNA 损伤介导了中国成年人尿金属与 2 型糖尿病患病率之间的关联。

Oxidative DNA damage mediates the association between urinary metals and prevalence of type 2 diabetes mellitus in Chinese adults.

机构信息

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

出版信息

Sci Total Environ. 2018 Jun 15;627:1327-1333. doi: 10.1016/j.scitotenv.2018.01.317. Epub 2018 Feb 7.

DOI:10.1016/j.scitotenv.2018.01.317
PMID:30857096
Abstract

Previous publications have indicated that some metals are associated with an increased prevalence of type 2 diabetes mellitus (T2DM); however, the mechanisms remain largely unknown. This study aimed to quantify the associations of oxidative DNA damage with urinary metals and prevalence of T2DM among the general population, and further to assess the role of oxidative DNA damage in mediating the association of urinary metals with prevalence of T2DM. Diagnoses of T2DM were performed clinically or by measuring fasting levels of plasma glucose ≥7.0mmol/L. Concentrations of urinary metals and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 2127 participants were measured using inductively coupled plasma-mass spectrometry and high-performance liquid chromatography. Relationships among urinary metals, 8-OHdG (a biomarker for oxidative DNA damage), and prevalence of T2DM were analyzed using mediation analysis. After adjusting for covariates, we found that the log-transformed levels of urinary copper, arsenic, selenium, molybdenum, and antimony were positively associated with prevalence of T2DM. Urinary 8-OHdG was not only positively correlated with copper, arsenic, selenium, and antimony in an upwardly trending, dose-responsive manner but was also positively associated with prevalence of T2DM (odds ratio (OR): 1.95; 95% CI: 1.17-3.24). Mediation analysis estimated that urinary 8-OHdG mediated 13.22% and 8.84% of associations between prevalence of T2DM and concentrations of urinary arsenic and antimony, respectively (all P value<0.05). Our findings suggested that urinary arsenic and antimony concentrations were associated with an increased prevalence of T2DM by a mechanism partly involving oxidative DNA damage.

摘要

先前的出版物表明,某些金属与 2 型糖尿病(T2DM)的患病率增加有关;然而,其机制在很大程度上仍不清楚。本研究旨在量化氧化 DNA 损伤与尿金属浓度之间的关联,以及氧化 DNA 损伤在介导尿金属与 T2DM 患病率之间的关联中的作用。T2DM 的诊断是通过临床或测量空腹血浆葡萄糖水平≥7.0mmol/L 来进行的。使用电感耦合等离子体质谱法和高效液相色谱法测量了 2127 名参与者的尿金属和 8-羟基-2'-脱氧鸟苷(8-OHdG)浓度。使用中介分析来分析尿金属、8-OHdG(氧化 DNA 损伤的生物标志物)与 T2DM 患病率之间的关系。在调整了协变量后,我们发现尿铜、砷、硒、钼和锑的对数转化水平与 T2DM 的患病率呈正相关。尿 8-OHdG 不仅与铜、砷、硒和锑呈正向相关,且呈上升趋势,呈剂量反应关系,而且与 T2DM 的患病率呈正相关(比值比(OR):1.95;95%置信区间(CI):1.17-3.24)。中介分析估计,尿 8-OHdG 分别介导了 T2DM 患病率与尿砷和锑浓度之间的 13.22%和 8.84%的关联(均 P 值<0.05)。我们的研究结果表明,尿砷和锑浓度与 T2DM 的患病率增加有关,其机制部分涉及氧化 DNA 损伤。

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